Alzheimer's Disease (AD) is a major national health problem affecting approximately 4 million individuals in this country. The etiology and pathogenesis of AD are not known. It has been postulated that trace elements neurotoxicity or imbalances play a role in the pathogenesis of AD. Our recent studies have shown an elevation of mercury (Hg) in the brains of AD patients. The source of this Hg is not known. Others have shown that dental amalgam fillings are a source of a large fraction of the Hg distributed in the body of normal individuals. There is considerable public and scientific concern about the safety of dental amalgams. The overall objective of this proposal is to study the relationship between brain Hg, dental amalgam fillings and AD. To do this we will study AD patients and control subjects during life and at autopsy. Each subject will have an assessment of dental amalgams locations, surface areas and length of time in the mouth, and an amalgam index will be determined. Following death the amount of Hg in the brain and other organs will be measured by neutron actuation analysis. The Hg levels in the brain will be correlated with the amalgam index and the number of senile plaque and neurofibrillary, tangles in AD and control. AD data will be obtained from subjects that are presently enrolled in two different funded studies at the University of Kentucky's Sanders-Brown Center on Aging. In Central Kentucky both control and AD subjects are part of ongoing NIA funded research projects at the Alzheimer's Disease Research Center. The School Sisters of Notre Dame located in Milwaukee, Wisconsin will be the second population which will provide both control and AD subjects for study. This cohort provides a homogenous group of females with relatively similar long-term life styles in the same geographic location. Over the five year period of the study we estimate we will be able to obtain oral and autopsy data on 125 control and 125 AD subjects. They study should provide a greater understanding of the role of dental amalgams and Hg in AD.